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Therefore, the SGLT2-i induced elevated ANG II levels could act through AT2R resulting in vasodilation, sodium excretion, antiproliferative and anti-inflammation effects ( In addition, it has also been observed a SGLT2-i induced ACE2/ANG(1-7) pathway activation that may play a role in cardioprotection by competing with ANG II and AT1R ( Furthermore, the SGLT2-i hybrid diuretic effect, which combines natriuresis and osmotic diuresis, might also have cardioprotective properties leading to preload and myocardial stretch reduction (the diuretic hypothesis) ( Therefore, SGLT2-i diuretic properties show a major advantage compared to thiazides and thiazides-like diuretics, which act on the Na + CL - -cotransporter in the distal convoluted tubule, or loop diuretics, which block the Na-K-2Cl co-transporter of both the Henle loop and the macula densa, making the macula insensitive to the increased tubular sodium coming from the Henle loop

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The CDC's diabetes research hub provides helpful context on how insulin dysregulation intersects with obesity and body composition, underscoring why this pathway must often be addressed before meaningful fat loss can occur

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Obesity alters adipose tissue macrophage iron content and tissue iron distribution

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